Ocular Manifestations in Juvenile Behçet's Disease: A Registry-Based Analysis from the AIDA Network.

INTRODUCTION: This study aims to characterize ocular manifestations of juvenile Behçet's disease (jBD). METHODS: This was a registry-based observational prospective study. All subjects with jBD from the Autoinflammatory Diseases Alliance (AIDA) Network BD Registry showing ocular manifestations before 18 years were enrolled. RESULTS: We included 27 of 1000 subjects enrolled in the registry (66.7% male patients, 45 affected eyes). The median (interquartile range [IQR]) age at ocular involvement was 14.2 (4.7) years. Uveitis affected 91.1% of eyes (anterior 11.1%, posterior 40.0%, panuveitis 40.0%), retinal vasculitis 37.8% and other manifestations 19.8%. Later onset (p = 0.01) and male predominance (p = 0.04) characterized posterior involvement. Ocular complications occurred in 51.1% of eyes. Patients with complications had earlier onset (p < 0.01), more relapses (p = 0.02) and more prolonged steroidal treatment (p = 0.02). The mean (standard deviation [SD]) central macular thickness (CMT) at the enrolment and last visit was 302.2 (58.4) and 293.3 (78.2) µm, respectively. Fluorescein angiography was pathological in 63.2% of procedures, with a mean (SD) Angiography Scoring for Uveitis Working Group (ASUWOG) of 17.9 (15.5). At the last visit, ocular damage according to the BD Overall Damage Index (BODI) was documented in 73.3% of eyes. The final mean (SD) best corrected visual acuity (BCVA) logMAR was 0.17 (0.47) and blindness (BCVA logMAR < 1.00 or central visual field ≤ 10°) occurred in 15.6% of eyes. At multivariate regression analysis, human leukocyte antigen (HLA)-B51 + independently predicted a + 0.35 change in the final BCVA logMAR (p = 0.01), while a higher BCVA logMAR at the first assessment (odds ratio [OR] 5.80; p = 0.02) independently predicted blindness. CONCLUSIONS: The results of this study may be leveraged to guide clinical practice and future research on this rare sight-threatening condition.

Structural Brain MR Imaging Alterations in Patients with Systemic Lupus Erythematous with and without Neuropsychiatric Events.

BACKGROUND AND PURPOSE: Systemic lupus erythematosus is a complex autoimmune disease known for its diverse clinical manifestations, including neuropsychiatric systemic lupus erythematosus, which impacts a patient's quality of life. Our aim was to explore the relationships among brain MR imaging morphometric findings, neuropsychiatric events, and laboratory values in patients with systemic lupus erythematosus, shedding light on potential volumetric biomarkers and diagnostic indicators for neuropsychiatric systemic lupus erythematosus. MATERIALS AND METHODS: Twenty-seven patients with systemic lupus erythematosus (14 with neuropsychiatric systemic lupus erythematosus, 13 with systemic lupus erythematosus), 24 women and 3 men (average age, 43 years, ranging from 21 to 62 years) were included in this cross-sectional study, along with 10 neuropsychiatric patients as controls. An MR imaging morphometric analysis, with the VolBrain online platform, to quantitatively assess brain structural features and their differences between patients with neuropsychiatric systemic lupus erythematosus and systemic lupus erythematosus, was performed. Correlations and differences between MR imaging morphometric findings and laboratory values, including disease activity scores, such as the Systemic Lupus Erythematosus Disease Activity Index and the Systemic Lupus International Collaborating Clinics Damage Index, were explored. An ordinary least squares regression analysis further explored the Systemic Lupus Erythematosus Disease Activity Index and Systemic Lupus International Collaborating Clinics Damage Index relationship with MR imaging features. RESULTS: For neuropsychiatric systemic lupus erythematosus and non-neuropsychiatric systemic lupus erythematosus, the brain regions with the largest difference in volumetric measurements were the insular central operculum volume (P value = .003) and the occipital cortex thickness (P = .003), which were lower in neuropsychiatric systemic lupus erythematosus. The partial correlation analysis showed that the most correlated morphometric features with neuropsychiatric systemic lupus erythematosus were subcallosal area thickness asymmetry (P < .001) and temporal pole thickness asymmetry (P = .011). The ordinary least squares regression analysis yielded an R 2 of 0.725 for the Systemic Lupus Erythematosus Disease Activity Index score, with calcarine cortex volume as a significant predictor, and an R 2 of 0.715 for the Systemic Lupus International Collaborating Clinics Damage Index score, with medial postcentral gyrus volume as a significant predictor. CONCLUSIONS: The MR imaging volumetric analysis, along with the correlation study and the ordinary least squares regression analysis, revealed significant differences in brain regions and their characteristics between patients with neuropsychiatric systemic lupus erythematosus and those with systemic lupus erythematosus, as well as between patients with different Systemic Lupus Erythematosus Disease Activity Index and Systemic Lupus International Collaborating Clinics Damage Index scores.

Orbital/ocular inflammatory involvement in VEXAS syndrome: Data from the international AIDA network VEXAS registry.

VEXAS syndrome is a recently described monogenic autoinflammatory disease capable of manifesting itself with a wide array of organs and tissues involvement. Orbital/ocular inflammatory manifestations are frequently described in VEXAS patients. The objective of this study is to further describe orbital/ocular conditions in VEXAS syndrome while investigating potential associations with other disease manifestations. In the present study, twenty-seven out of 59 (45.8 %) VEXAS patients showed an inflammatory orbital/ocular involvement during their clinical history. The most frequent orbital/ocular affections were represented by periorbital edema in 8 (13.6 %) cases, episcleritis in 5 (8.5 %) patients, scleritis in 5 (8.5 %) cases, uveitis in 4 (6.8 %) cases, conjunctivitis in 4 (6.8 %) cases, blepharitis in 3 (5.1 %) cases, orbital myositis in 2 (3.4 %) cases. A diagnosis of systemic immune-mediated disease was observed in 15 (55.6 %) cases, with relapsing polychondritis diagnosed in 12 patients. A significant association was observed between relapsing polychondritis and orbital/ocular involvement in VEXAS syndrome (Relative Risk: 2.37, 95 % C.I. 1.03-5.46, p = 0.048). Six deaths were observed in the whole cohort of patients after a median disease duration of 1.2 (IQR=5.35) years, 5 (83.3 %) of which showed orbital/ocular inflammatory involvement. In conclusion, this study confirms that orbital/ocular inflammatory involvement is a common finding in VEXAS patients, especially when relapsing polychondritis is diagnosed. This makes ophthalmologists a key figure in the diagnostic process of VEXAS syndrome. The high frequency of deaths observed in this study seems to suggest that patients with orbital/ocular involvement may require increased attention and more careful follow-up.

Agreement between local and central anti-synthetase antibodies detection: results from the Classification Criteria of Anti-Synthetase Syndrome project biobank.

OBJECTIVES: The CLASS (Classification Criteria of Anti-Synthetase Syndrome) project is a large international multicentre study that aims to create the first data-driven anti-synthetase syndrome (ASSD) classification criteria. Identifying anti-aminoacyl tRNA synthetase antibodies (anti-ARS) is crucial for diagnosis, and several commercial immunoassays are now available for this purpose. However, using these assays risks yielding false-positive or false-negative results, potentially leading to misdiagnosis. The established reference standard for detecting anti-ARS is immunoprecipitation (IP), typically employed in research rather than routine autoantibody testing. We gathered samples from participating centers and results from local anti-ARS testing. As an "ad-interim" study within the CLASS project, we aimed to assess how local immunoassays perform in real-world settings compared to our central definition of anti-ARS positivity. METHODS: We collected 787 serum samples from participating centres for the CLASS project and their local anti-ARS test results. These samples underwent initial central testing using RNA-IP. Following this, the specificity of ARS was reconfirmed centrally through ELISA, line-blot assay (LIA), and, in cases of conflicting results, protein-IP. The sensitivity, specificity, positive likelihood ratio and positive and negative predictive values were evaluated. We also calculated the inter-rater agreement between central and local results using a weighted κ co-efficient. RESULTS: Our analysis demonstrates that local, real-world detection of anti-Jo1 is reliable with high sensitivity and specificity with a very good level of agreement with our central definition of anti-Jo1 antibody positivity. However, the agreement between local immunoassay and central determination of anti-non-Jo1 antibodies varied, especially among results obtained using local LIA, ELISA and "other" methods. CONCLUSIONS: Our study evaluates the performance of real-world identification of anti-synthetase antibodies in a large cohort of multi-national patients with ASSD and controls. Our analysis reinforces the reliability of real-world anti-Jo1 detection methods. In contrast, challenges persist for anti-non-Jo1 identification, particularly anti-PL7 and rarer antibodies such as anti-OJ/KS. Clinicians should exercise caution when interpreting anti-synthetase antibodies, especially when commercial immunoassays test positive for non-anti-Jo1 antibodies.

Power Doppler signal at the enthesis and bone erosions are the most discriminative OMERACT ultrasound lesions for SpA: results from the DEUS (Defining Enthesitis on Ultrasound in Spondyloarthritis) multicentre study.

OBJECTIVES: To assess, in spondyloarthritis (SpA), the discriminative value of the Outcome Measures in Rheumatology (OMERACT) ultrasound lesions of enthesitis and their associations with clinical features in this population. METHODS: In this multicentre study involving 20 rheumatology centres, clinical and ultrasound examinations of the lower limb large entheses were performed in 413 patients with SpA (axial SpA and psoriatic arthritis) and 282 disease controls (osteoarthritis and fibromyalgia). 'Active enthesitis' was defined as (1) power Doppler (PD) at the enthesis grade ≥1 plus entheseal thickening and/or hypoechoic areas, or (2) PD grade >1 (independent of the presence of entheseal thickening and/or hypoechoic areas). RESULTS: In the univariate analysis, all OMERACT lesions except enthesophytes/calcifications showed a significant association with SpA. PD (OR=8.77, 95% CI 4.40 to 19.20, p<0.001) and bone erosions (OR=4.75, 95% CI 2.43 to 10.10, p<0.001) retained this association in the multivariate analysis. Among the lower limb entheses, only the Achilles tendon was significantly associated with SpA (OR=1.93, 95% CI 1.30 to 2.88, p<0.001) in the multivariate analyses. Active enthesitis showed a significant association with SpA (OR=9.20, 95% CI 4.21 to 23.20, p<0.001), and unlike the individual OMERACT ultrasound lesions it was consistently associated with most clinical measures of SpA disease activity and severity in the regression analyses. CONCLUSIONS: This large multicentre study assessed the value of different ultrasound findings of enthesitis in SpA, identifying the most discriminative ultrasound lesions and entheseal sites for SpA. Ultrasound could differentiate between SpA-related enthesitis and other forms of entheseal pathology (ie, mechanical enthesitis), thus improving the assessment of entheseal involvement in SpA.

Psychometric properties of patient global assessment in Psoriatic Arthritis: a systematic literature review.

OBJECTIVE: Patient Global Assessment (PtGA) is a patient-reported outcome (PRO) that reflects patients' judgment of health/disease activity (DA). The objective of this systematic literature review was to assess the psychometric properties of PtGA in Psoriatic Arthritis (PsA). METHODS: Research articles reporting the assessment of psychometric properties of PtGA in PsA, listed in PubMed, extracted according to the OMERACT Filter 2.1 and the COSMIN terminology, were selected. Validity was assessed for comprehensiveness (content), correlation with other DA instruments (construct) and with quality of life measurements (criterion). A meta-analysis regarding construct validity was performed. Correlations between PtGA variations and other indices' variations (external responsiveness) and PtGA variations after treatment (internal responsiveness) were collected. Data on the formulation of the PtGA and its discordance with physician global assessment (PhGA) were also collected. RESULTS: Of 60 articles analysed (17453 patients), 44 were observational studies and 16 were trials. PtGA was assessed through 27 different formulations. In all the retrieved studies PtGA assessed DA, in 3 global health status. The correlation between PtGA and PROs was strong (R>0.50), while with other DA indices and PhGA, it ranged from weak to moderate (R=0.20-0.50), and three studies described a positive discordance (PtGA > PhGA). Responsiveness, assessed in 24 studies, showed a strong correlation (R=0.51-0.52) with joint count index variations. CONCLUSION: PtGA is a valid and responsive tool in PsA. Correlations were higher with PROs and weaker with DA composite indices and PhGA. PhGA was usually scored lower than PtGA. A standardized formulation of PtGA would be useful.

Clinical patterns of disease: From early systemic lupus erythematosus to late-onset disease.

Systemic lupus erythematosus (SLE) is a complex disease with an insidious clinical presentation. In up to half of the cases, SLE onset is characterized by clinical and serological manifestations that, although specific, are insufficient to fulfill the classification criteria. This condition, called incomplete SLE, could be as challenging as the definite and classifiable SLE and requires to be treated according to the severity of clinical manifestations. In addition, an early SLE diagnosis and therapeutic intervention can positively influence the disease outcome, including remission rate and damage accrual. After diagnosis, the disease course is relapsing-remitting for most patients. Time in remission and cumulative glucocorticoid exposure are the most important factors for prognosis. Therefore, timely identification of SLE clinical patterns may help tailor the therapeutic intervention to the disease course. Late-onset SLE is rare but more often associated with delayed diagnosis and a higher incidence of comorbidities, including Sjogren's syndrome. This review focuses on the SLE disease course, providing actionable strategies for early diagnosis, an overview of the possible clinical patterns of SLE, and the clinical variation associated with the different age-at-onset SLE groups.

Therapeutic Strategies and Outcomes in Neuropsychiatric Systemic Lupus Erythematosus: An International Multicenter Retrospective Study.

OBJECTIVES: The management of neuropsychiatric systemic lupus erythematosus (NPSLE) poses considerable challenges due to limited clinical trials. Therapeutic decisions are customized based on suspected pathogenic mechanisms and symptom severity. This study aimed to investigate therapeutic strategies and disease outcome for patients with NPSLE experiencing their first neuropsychiatric (NP) manifestation. METHODS: This retrospective cohort study defined NP events according to the American College of Rheumatology case definition, categorizing them into three clusters: central/diffuse, central/focal and peripheral. Clinical judgment and a validated attribution algorithm were used for NP event attribution. Data included demographic variables, SLE disease activity index, cumulative organ damage, and NP manifestation treatments. The clinical outcome of all NP events was determined by a physician seven-point Likert scale. Predictors of clinical improvement/resolution were investigated in a multivariable logistic regression analysis. RESULTS: The analysis included 350 events. Immunosuppressants and corticosteroids were more frequently initiated/escalated for SLE-attributed central diffuse or focal NP manifestations. At 12 months of follow-up, 64% of patients showed a clinical improvement in NP manifestations. Focal central events and SLE-attributed manifestations correlated with higher rates of clinical improvement. Patients with NP manifestations attributed to SLE according to clinical judgment and treated with immunosuppressants had a significantly higher probability of achieving clinical response (OR 2.55, 95%CI 1.06-6.41, p= 0.04). Age at diagnosis and focal central events emerged as additional response predictors. CONCLUSION: NP manifestations attributed to SLE by clinical judgment and treated with immunosuppressants demonstrated improved 12-month outcomes. This underscores the importance of accurate attribution and timely diagnosis of NPSLE.

Quality of Life in Systemic Lupus Erythematosus and Other Chronic Diseases: Highlighting the Amplified Impact of Depressive Episodes.

BACKGROUND: Extensive research has explored SLE's impact on health-related quality of life (H-QoL), especially its connection with mental wellbeing. Recent evidence indicates that depressive syndromes significantly affect H-QoL in SLE. This study aims to quantify SLE's impact on H-QoL, accounting for comorbid depressive episodes through case-control studies. METHODS: A case-control study was conducted with SLE patients (meeting the ACR/EULAR 2019 criteria of age ≥ 18). The control group was chosen from a community database. H-QoL was measured with the SF-12 questionnaire, and PHQ-9 was used to assess depressive episodes. RESULTS: SLE significantly worsened H-QoL with an attributable burden of 5.37 ± 4.46. When compared to other chronic diseases, only multiple sclerosis had a worse impact on H-QoL. Major depressive episodes had a significant impact on SLE patients' H-QoL, with an attributable burden of 9.43 ± 5.10, similar to its impact on solid cancers but greater than its impact on other diseases. CONCLUSIONS: SLE has a comparable impact on QoL to serious chronic disorders. Concomitant depressive episodes notably worsened SLE patients' QoL, exceeding other conditions, similar to solid tumors. This underscores the significance of addressing mood disorders in SLE patients. Given the influence of mood disorders on SLE outcomes, early identification and treatment are crucial.

Assessment and personalised advice for fatigue in systemic lupus erythematosus using an innovative digital tool: the Lupus Expert system for the Assessment of Fatigue (LEAF) study.

BACKGROUND: Fatigue is reported as the most prevalent symptom by patients with systemic lupus erythematosus (SLE). Fatigue management is complex due to its multifactorial nature. The aim of the study was to assess the usefulness of an innovative digital tool to manage fatigue in SLE, in a completely automated manner. METHODS: The «Lupus Expert System for Assessment of Fatigue¼ (LEAF) is free digital tool which measures the intensity and characteristics of fatigue and assesses disease activity, pain, insomnia, anxiety, depression, stress, fibromyalgia and physical activity using validated patient-reported instruments. Then, LEAF automatically provides personalised feedback and recommendations to cope with fatigue. RESULTS: Between May and November 2022, 1250 participants with SLE were included (95.2% women, median age 43yo (IQR: 34-51)). Significant fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue <34) was reported by 78.9% of patients. In univariate analysis, SLE participants with fatigue were more likely to be women (p=0.01), perceived their disease as more active (p<0.0001), had higher levels of pain (p<0.0001), anxiety (p<0.0001), depression (p<0.0001), insomnia (p<0.0001), stress (p<0.0001) and were more likely to screen for fibromyalgia (p<0.0001), compared with patients without significant fatigue. In multivariable analysis, parameters independently associated with fatigue were insomnia (p=0.0003), pain (p=0.002), fibromyalgia (p=0.008), self-reported active SLE (p=0.02) and stress (p=0.045). 93.2% of the participants found LEAF helpful and 92.3% would recommend it to another patient with SLE. CONCLUSION: Fatigue is commonly severe in SLE, and associated with insomnia, pain, fibromyalgia and active disease according to patients' perspective. Our study shows the usefulness of an automated digital tool to manage fatigue in SLE.

Organ damage is a major determinant of work productivity impairment in Behçet's Syndrome: a post-hoc analysis of the BODI validation study.

OBJECTIVES: To evaluate the prevalence, magnitude, and potential determinants of work productivity impairment in patients with Behçet's Syndrome (BS), focusing on the role of irreversible organ damage. METHODS: A post-hoc analysis of the BS overall damage index (BODI) prospective validation study was performed. Demographics and clinical features were recorded in all patients. The Work Productivity and Activity Impairment: General Health (WPAI: GH) questionnaire was administered to assess the work limitation and the BODI to measure organ damage. The independent effect of BS features on WPAI: GH outcomes was evaluated by regression analysis. RESULTS: Out of 148 patients, 34.5% were unemployed, with age (OR 1.035) and BODI score (OR 1.313 for 1-unit increase) as the only factors significantly (p< 0.05) associated with the unemployment state. An overall work impairment was reported in about 64.2% of the employed patients. Indeed, 22.7% reported missing work h due to their health (absenteeism), with a mean time loss of 34.4%; whereas 60.2% declared a reduced performance at work because of their health (presenteeism), with a mean productivity impairment of 45.4%. Ocular damage was associated with absenteeism (ß 0.225); female sex (ß 0.260), physician global assessment of disease activity (ß 0.502) and an increased BODI score (ß 0.166 for 1-point increase) with presenteeism; fibromyalgia (ß 0.246), physician global assessment (ß 0.469), and musculoskeletal damage (ß 0.325) with overall work impairment. CONCLUSIONS: Disease activity and organ damage accrual remarkably affect work productivity in BS patients. Achieving remission and preventing damage accrual are crucial and complementary objectives.

Molecular profiling of clinical remission in psoriatic arthritis reveals dysregulation of FOS and CCDC50 genes: a gene expression study.

Background: In psoriatic arthritis (PsA), the primary goal of treatment is clinical remission. This study aimed to characterize the molecular profile underlying the induced clinical remission in patients with PsA, comparing the remission state and the healthy condition. Methods: Whole blood transcriptomic analysis was performed on groups of 14 PsA patients in TNFi-induced clinical remission (DAPSA ≤ 4), 14 PsA patients with active disease (DAPSA > 14), and 14 healthy controls (HCs). Then, all differentially expressed genes (DEGs) derived from remission vs. HC comparison were analyzed for functional and biological characteristics by bioinformatics software. The gene expression of 12 genes was then validated by RT-qPCR in an extended cohort of 39 patients in clinical remission, 40 with active disease, and 40 HCs. Results: The transcriptomic analysis of PsA remission vs. HCs highlighted the presence of 125 DEGs, and out of these genes, 24 were coding genes and showed a great involvement in immune system processes and a functional network with significant interactions. The RT-qPCR validation confirming the down- and upregulation of FOS (FC -2.0; p 0.005) and CCDC50 (FC +1.5; p 0.005) genes, respectively, in line with their role in orchestrating inflammation and bone metabolism processes, may be related to PsA pathophysiology. Conclusion: The transcriptomic profile of clinical remission in PsA is similar to a healthy condition, but not identical, differing for the expression of FOS and CCDC50 genes, which appears to play a key role in its achievement.

Effects of cytotoxic T-lymphocyte-associated protein 4 compared to TNF inhibitors on lipid profile: Results from an observational multicentre rheumatoid arthritis cohort.

AIM: To evaluate the impact of selective cytotoxic T-lymphocyte-associated protein 4 (CTLA-4Ig) compared to tumor necrosis factor inhibitors (TNFi) on cardiovascular (CV) clinical and laboratory outcomes in patients with rheumatoid arthritis (RA). METHODS: We performed a prospective observational multicenter study of RA patients included in the "Cardiovascular Obesity and Rheumatic DISease (CORDIS)" Study Group database, collecting demographic, clinical, and laboratory data of those starting a CTLA-4Ig or TNFi at baseline, 6-month, and 12-month follow-up. RESULTS: Of the 206 RA patients without previous CV events enrolled in the study, 64 received a CTLA-4Ig and 142 a TNFi. The two groups did not differ in age, gender, or smoking habits, and the prevalence of hypertension, diabetes, and metabolic syndrome was similar. Over a follow-up period of 12 months, although no significant differences were found in the disease activity course, we observed that LDL cholesterol levels slightly decreased only in the CTLA-4Ig-treated patients. CONCLUSIONS: Patients treated with both CTLA-4Ig and TNFi did not differ in disease activity response and changes in traditional CV risk factors after 12 months of treatment. However, CTL-A-4Ig treatment is associated with a favorable change in lipid profile at 12-month follow-up.

Effect of anti-P ribosomal and anti-NR2 antibodies on depression and cognitive processes in SLE: an integrated clinical and functional MRI study.

OBJECTIVES: To explore the effects of anti-ribosomal P protein (anti-P) and anti-N-methyl-D-aspartic acid receptor subunit 2 (anti-NR2) autoantibodies on depression and cognitive dysfunction and their relationships with functional brain connectivity in SLE. METHODS: This cross-sectional study included adult patients who fulfilled the American College of Rheumatology/European Alliance of Associations for Rheumatology 2019 SLE criteria. Anti-P and anti-NR2 were quantified using ELISA. A 1-hour battery of neuropsychological testing interpreted by a neuropsychologist explored depressive symptoms (Center for Epidemiologic Studies Depression Scale, CES-D), cognitive domains and quality of life (SF-12). Resting-state functional connectivity (rs-fc) MRI analysis was performed within 1 month, and region-of-interest to region-of-interest (ROI-to-ROI) analyses with the graph theory were performed. RESULTS: Thirty-three patients with SLE (9% male) were enrolled, mean age (SD) of 43.5 (14) years and median disease duration of 10.4 years (2.9-25.4). Anti-P was positive in 6 (18.2%) and anti-NR2 in 14 (42.4%) patients. Depressive symptoms were found in 14 (42.4%) patients using the CES-D (range 0-51). After correction for age, disease duration, disease activity and white matter lesion load, the CES-D score was independently associated with anti-P serum level (ß=0.32; p=0.049) and prednisone daily dose (ß=0.38; p=0.023). Nineteen patients (57.6%) showed at least a cognitive test alteration, but no significant association with autoantibodies was found. The rs-fc MRI analysis revealed an independent association between the anti-P serum levels and many altered brain ROI properties but no anti-NR2 and prednisone effects on the cerebral network. CONCLUSIONS: Anti-P was associated with brain network perturbation, which may be responsible for depressive symptoms in patients with SLE.

Unfolding dermatologic spectrum of Behçet's disease in Italy: real-life data from the International AIDA Network Behçet's disease Registry.

Behçet's disease (BD) is a heterogeneous multifactorial autoinflammatory disease characterized by a plethora of clinical manifestations. Cutaneous lesions are considered hallmarks of the disease. However, their evolution over time and a thorough description are scarcely reported in non-endemic regions. The aim of this study was to detail BD skin manifestations and their evolution over time in Italy, as well as the dermatological prognostic impact of specific cutaneous features in long-standing disease. Data were collected in a double fashion, both retrospectively and prospectively, from the AutoInflammatory Disease Alliance (AIDA) international registry dedicated to BD, between January 2022 and December 2022. A total of 458 Italian patients were included. When assessing skin manifestations course, the constant or sporadic presence or absence of cutaneous involvement between onset and follow-up was considered. Oral ulcers (OU) (88.4%) and genital ulcers (GU) (52.6%), followed by skin involvement (53.7%) represented the most common presenting mucocutaneous manifestations at disease onset. Up to the time of enrolment into the AIDA registry, 411 (93.8%) patients had suffered from OU and 252 (57.9%) from GU; pseudofolliculitis (PF) accounted for the most common skin manifestation (170 patients, 37.1%), followed by erythema nodosum (EN) (102 patients, 22.3%), skin ulcers (9 patients, 2%) and pyoderma gangrenosum (4 patients, 0.9%). A prospective follow-up visit was reported in 261/458 patients; 24/148 (16.2%) subjects with skin involvement as early as BD onset maintained cutaneous lesions for the entire period of observation, while 120 (44.1%) patients suffered from sporadic skin involvement. Conversely, 94/113 (83.2%) with no skin involvement at disease onset did not develop skin lesions thereafter. At follow-up visits, cutaneous involvement was observed in 52 (20%) patients, with a statistically significant association between PF and constant skin involvement (p = 0.031). BD in Italy is characterized by a wide spectrum of clinical presentations and skin manifestations in line with what is described in endemic countries. Patients with skin disease at the onset are likely to present persistent cutaneous involvement thereafter; mucocutaneous lesions observed at the onset, especially PF, could represent a warning sign for future persistent skin involvement requiring closer dermatological care.

Prevalence, characteristics, and knowledge related to photosensitivity in patients with lupus erythematosus: the international PHOTOLUP study.

OBJECTIVES: To assess the prevalence, characteristics and knowledge about photosensitivity and the use of photoprotective measures in an international cohort of cutaneous and systemic lupus erythematosus patients. METHODS: We conducted an international, cross-sectional study based on a 46-question web-based survey including patients with medically confirmed LE conducted between November 2021 and April 2022. RESULTS: 600 patients with lupus erythematosus (94% female, median age: 41 years [IQR: 33-51]) from 50 countries were included. A history of photosensitivity was reported by 389/600 (64.8%) patients. Photosensitivity was associated with the presence of other cutaneous involvement (OR = 3.8; 95%CI 2.5-5.7; p < 0.001) and differed according to the area of habits and level of education (p < 0.001, for all). Photosensitivity was characterized by a wide range of clinical manifestations (both cutaneous and systemic symptoms in 56.1% and systemic symptoms only in 29.8% of patients). Fatigue was the most frequently reported systemic manifestation (82.3%). Overall, 559/600 (93%) patients were aware of the detrimental role of UV exposure in lupus erythematosus, but 160/480 (33.3%) were unaware of the importance of photoprotective measures, including 90/310 (29%) among those with photosensitivity. CONCLUSION: A high rate of self-reported photosensitivity characterize lupus erythematosus patients. Photosensitivity frequently includes subjective features, which makes it difficult to evaluate in clinical practice. As fatigue is frequent in LE, further study is needed to clarify its causal link with UV exposure. About one-third of lupus erythematosus patients are unaware of the importance of photoprotective measures. This should be improved through more frequent and targeted awareness interventions.

The Challenging Differentiation of Psoriatic Arthritis from Other Arthropathies and Nonspecific Arthralgias in Patients with Psoriasis: Results of a Cross-Sectional Rheumatologic Assessment of a Large Dermatologic Cohort.

Aiming to identify the potential challenges in the classification of musculoskeletal manifestations in patients with psoriasis (PsO), this study analyzed the outcomes of a cross-sectional rheumatologic assessment of 1057 PsO patients. In total, 209 had a previous diagnosis of psoriatic arthritis (PsA). Out of the remaining 848 subjects, 293 (35%) were classified as suspected PsA cases according to the rheumatologist's judgment and/or Early PsA Screening Questionnaire score (EARP) ≥ 3. However, only 14% received a PsA diagnosis, 49% had a PsA-alternative diagnosis, and the remaining 37% had nonspecific arthralgias. Most of the newly diagnosed PsA patients had a symptoms duration ≥1 year (72%) and moderate disease activity (55%) with active oligoarthritis (85%), dactylitis, or enthesitis (35%) as the most frequent clinical pattern. The most frequent PsA-alternative diagnoses were osteoarthritis and fibromyalgia (44% and 41%). The only factors with significant (p < 0.05) utility in discriminating PsA from other diseases and nonspecific arthralgias were young age and EARP score with a history of morning stiffness, swollen joints, or dactylitis. These results demonstrated a high prevalence of suspected musculoskeletal symptoms in PsO patients, with, however, only a small proportion due to PsA. Close collaboration between the dermatologist and rheumatologist plays a crucial role in the differential diagnosis of PsA, as well as in monitoring nonspecific arthralgias for the potential transition to overt PsA.

A patient-driven registry on Behçet's disease: the AIDA for patients pilot project.

Introduction: This paper describes the creation and preliminary results of a patient-driven registry for the collection of patient-reported outcomes (PROs) and patient-reported experiences (PREs) in Behçet's disease (BD). Methods: The project was coordinated by the University of Siena and the Italian patient advocacy organization SIMBA (Associazione Italiana Sindrome e Malattia di Behçet), in the context of the AIDA (AutoInflammatory Diseases Alliance) Network programme. Quality of life, fatigue, socioeconomic impact of the disease and therapeutic adherence were selected as core domains to include in the registry. Results: Respondents were reached via SIMBA communication channels in 167 cases (83.5%) and the AIDA Network affiliated clinical centers in 33 cases (16.5%). The median value of the Behçet's Disease Quality of Life (BDQoL) score was 14 (IQR 11, range 0-30), indicating a medium quality of life, and the median Global Fatigue Index (GFI) was 38.7 (IQR 10.9, range 1-50), expressing a significant level of fatigue. The mean Beliefs about Medicines Questionnaire (BMQ) necessity-concern differential was 0.9 ± 1.1 (range - 1.8-4), showing that the registry participants prioritized necessity belief over concerns to a limited extent. As for the socioeconomic impact of BD, in 104 out of 187 cases (55.6%), patients had to pay from their own pocket for medical exams required to reach the diagnosis. The low family socioeconomic status (p < 0.001), the presence of any major organ involvement (p < 0.031), the presence of gastro-intestinal (p < 0.001), neurological (p = 0.012) and musculoskeletal (p = 0.022) symptoms, recurrent fever (p = 0.002), and headache (p < 0.001) were associated to a higher number of accesses to the healthcare system. Multiple linear regression showed that the BDQoL score could significantly predict the global socioeconomic impact of BD (F = 14.519, OR 1.162 [CI 0.557-1.766], p < 0.001). Discussion: Preliminary results from the AIDA for Patients BD registry were consistent with data available in the literature, confirming that PROs and PREs could be easily provided by the patient remotely to integrate physician-driven registries with complementary and reliable information.

Brain-reactive autoantibodies in neuropsychiatric systemic lupus erythematosus.

Introduction: The pathogenesis of neuropsychiatric systemic lupus erythematosus (NPSLE) is widely unknown, and the role of autoantibodies is still undetermined. Methods: To identify brain-reactive autoantibodies possibly related to NPSLE, immunofluorescence (IF) and transmission electron microscopy (TEM) on rat and human brains were performed. ELISA was used to reveal the presence of known circulating autoantibodies, while western blot (WB) was applied to characterize potential unknown autoantigen(s). Results: We enrolled 209 subjects, including patients affected by SLE (n=69), NPSLE (n=36), Multiple Sclerosis (MS, n=22), and 82 age- and gender-matched healthy donors (HD). Autoantibody reactivity by IF was observed in almost the entire rat brain (cortex, hippocampus, and cerebellum) using sera from NPSLE and SLE patients and was virtually negative in MS and HD. NPSLE showed higher prevalence (OR 2.4; p = 0.047), intensity, and titer of brain-reactive autoantibodies than SLE patients. Most of the patient sera with brain-reactive autoantibodies (75%) also stained human brains. Double staining experiments on rat brains mixing patients' sera with antibodies directed against neuronal (NeuN) or glial markers showed autoantibody reactivity restricted to NeuN-containing neurons. Using TEM, the targets of brain-reactive autoantibodies were located in the nuclei and, to a lesser extent, in the cytoplasm and mitochondria. Given the high degree of colocalization between NeuN and brain-reactive autoantibodies, we assumed NeuN was a possible autoantigen. However, WB analysis with HEK293T cell lysates expressing or not expressing the gene encoding for NeuN protein (RIBFOX3) showed that patients' sera carrying brain-reactive autoantibodies did not recognize the NeuN corresponding band size. Among the panel of NPSLE-associated autoantibodies (e.g., anti-NR2, anti-P-ribosomal protein, antiphospholipid) investigated by ELISA assay, only the anti-ß2-glycoprotein-I (aß2GPI) IgG was exclusively found in those sera containing brain-reactive autoantibodies. Conclusion: In conclusion, SLE and NPSLE patients possess brain-reactive autoantibodies but with higher frequency and titers found in NPSLE patients. Although many target antigens of brain-reactive autoantibodies are still undetermined, they likely include ß2GPI.

Early and Late Response and Glucocorticoid-Sparing Effect of Belimumab in Patients with Systemic Lupus Erythematosus with Joint and Skin Manifestations: Results from the Belimumab in Real Life Setting Study-Joint and Skin (BeRLiSS-JS).

AIM: To assess the efficacy of belimumab in joint and skin manifestations in a nationwide cohort of patients with SLE. METHODS: All patients with skin and joint involvement enrolled in the BeRLiSS cohort were considered. Belimumab (intravenous, 10 mg/kg) effectiveness in joint and skin manifestations was assessed by DAS28 and CLASI, respectively. Attainment and predictors of DAS28 remission (<2.6) and LDA (≥2.6, ≤3.2), CLASI = 0, 1, and improvement in DAS28 and CLASI indices ≥20%, ≥50%, and ≥70% were evaluated at 6, 12, 24, and 36 months. RESULTS: DAS28 < 2.6 was achieved by 46%, 57%, and 71% of patients at 6, 12, and 24 months, respectively. CLASI = 0 was achieved by 36%, 48%, and 62% of patients at 6, 12, and 24 months, respectively. Belimumab showed a glucocorticoid-sparing effect, being glucocorticoid-free at 8.5%, 15.4%, 25.6%, and 31.6% of patients at 6, 12, 24, and 36 months, respectively. Patients achieving DAS-LDA and CLASI-50 at 6 months had a higher probability of remission at 12 months compared with those who did not (p = 0.034 and p = 0.028, respectively). CONCLUSIONS: Belimumab led to clinical improvement in a significant proportion of patients with joint or skin involvement in a real-life setting and was associated with a glucocorticoid-sparing effect. A significant proportion of patients with a partial response at 6 months achieved remission later on during follow-up.